Minor Ailment Pharmacology

Question 1

What is the MOA of decongestants and what are some examples?

Answer 1

Decongestants are A-1 adrenergic receptor agonists that act in the nasal mucosa to produce vasoconstriction

Vasoconstriction decreases resistance to airflow and improves ventilation by decreasing the volume of nasal mucosa and reduced delivery and secretion of fluids to the nasal mucosa

Examples: ephedrine, pseudophedrine, and phenylephrine

Question 2

What are the differences between ephedrine, pseudoephedrine, and phenylephrine?

Answer 2

Ephedrine → directly stimulates A-1 and B adrenergic receptors so it causes bronchial relaxation, increased HR and contractility, and enhances release of NE from sympathetic neurons

Pseudoephedrine → directly stimulates A-1 and B receptors but is less potent in producing tachycardia, increasing BP and CNS activation

Phenylephrine → selective A-1 agonist

Question 3

What is the difference in the onset of action for oral vs topical decongestants?

Answer 3

Oral = 30 min

Topical = 5-10 min

Topical products also come in long acting (dosed 2x day) and short acting (dosed every 4h) versions

Question 4

What is the MOA of an antitussive and what are some examples?

Answer 4

Acts on the medulla to increase cough threshold and suppress cough

Codeine → acts on opioid receptors in the medullary cough center, little effectiveness at OTC doses and AEs include sedation and constipation

Dextromethorphan → chemically similar to codeine with no analgesic or euphoric properties, does not act on opioid receptors but acts centrally to elevate threshold for coughing, fewer side effects than codeine

Question 5

What is the MOA for expectorants and what is an example?

Answer 5

MOA: thought to stimulate respiratory tract secretions, thereby increasing respiratory fluid volumes and decreasing mucous viscosity; should help get phlegm out by coughing

Guaifenesin → little evidence for efficacy and no evidence for adverse effects or drug interactions

Question 6

Where is histamine primarily stored?

Answer 6

Mast cells

Mast cells are found in large numbers in the skin, bronchial mucosa, intestinal mucosa, and basophils

Question 7

Explain the mechanism histamine being released from storage granules in an allergic response

Answer 7

1. Antigen interacts with IgE antibodies on the surface of mast cells
2. Leads to the production of IP3 which increases cellular calcium
3. Calcium causes exocytosis of the content of secretory granules
4. This leads to the release of histamine, as well as release and production of other allergic mediators like leukotrienes

Question 8

Where are H1 receptors found and what do they do?

Answer 8

H1 receptors are distributed widely in CNS and periphery, particularly on smooth muscle and endothelial cells

Many of the common effects of histamine are due to activation of the H1 receptors (itching, stimulation of nasal secretion, sedation associated with antihistamines)

Question 9

Where are H2 receptors found?

Answer 9

Distributed in gastric parietal cells, cardiac muscle, mast cells and in the CNS

Question 10

What are H3 receptors?

Answer 10

Auto-receptors on histamine-containing neurons

activation inhibits further histamine release

Question 11

What are the vascular and other effects of Histamine?

Answer 11

• dilation of resistance vessels - involves H1 and H2
• constriction of veins due to activation of H1 receptors on vascular smooth muscle, contributes to extravastion of fluid and edema
• Increased capillary permeability which also contributes to edema
• Large amounts of histamine (like in anaphylaxis) cause profound reduction in blood pressure due to vasodilation and plasma escape from circulation

Other:

• altered cardiac contractility and electrical conductance (via H1 and H2)
• contraction of non-vascular smooth muscle (H1) contributes to bronchoconstriction in patients with asthma
• wheal formation, itching, pain

Question 12

What are the two main differences between 1st and 2nd generation of antihistamines?

Answer 12

1. 1st gen can cross the blood brain barrier and 2nd gen cannot
2. 1st gen are not selective for H1 receptors and also block muscarinic receptors giving anticholinergic side effects

Question 13

What is an eicosandoid?

Answer 13

Lipid signalling molecule related to or derived from arachidonic acid

Net effect on a particular tissue involves both the number and type of eicosanoid receptor and the type and concentration of eicosanoid present

Question 14

What is a prostanoid?

Answer 14

Primarily derived via the actions of COX (enzyme that converts arachidonic acid into PGH2)

Other prostanoids are metabolites of PGH2

Question 15

What is a leukotriene?

Answer 15

Derived from HPETE which is produced from arachidonic acid by lipoxygenase, additional synthase, hydrolase, and dipeptidase enzymes then convert HPETE into additional leukotrienes

Question 16

How does inflammation and swelling happen? What is the purpose?

Answer 16

Inflammation → release of local inflammatory mediators and accumulation of neutrophils as the primary WBC

Swelling → movement of plasma into the area of inflammation

This dilutes toxins, initiates blood clotting to prevent anything from reaching the rest of the body

Question 17

What does a local inflammatory hormone do and what are some examples?

Answer 17

Some can directly stimulate sensory pain neurons (histamine, bradykinins)

Some reduce threshold for firing (histamine, prostaglandins)

Question 18

What is the MOA of acetaminophen?

Answer 18

Centrally produces a fever-reducing activity via inhibition of COX in the thermoregulatory center

Inhibits synthesis and release of prostaglandins in the thermoregulatory center of the anterior hypothalamus to reverse fever-inducing actions

Question 19

What is the MOA for NSAIDs?

Answer 19

NSAIDs inhibit COX to prevent conversion of arachidonic acid to PGH2 thus preventing subsequent prostaglandin production; anti-inflammatory effects but not related to cortisol

Question 20

What are the differences between ibuprofen and naproxen?

Answer 20

Ibuprofen is better tolerated than aspirin, has a half life of 2-4 hours, and is equally potent for COX1 and COX2 receptors

Naproxen has a longer half-life at ~14 hours and is slightly COX1 selective

Question 21

How do corticosteroids have anti-inflammatory actions and what else are they used for?

Answer 21

Corticosteroids inhibit phospholipase A2, the first enzyme in the arachidonic acid cascade

Inhibition of arachidonic acid also inhibits the production of its metabolites including prostaglandins, bradykinins and leukotrienes

Also used for disease states involving the immune system (autoimmune disorders and any inflammatory condition including acute and chronic pain)

Question 22

How do H2 histamine receptor antagonists reduce stomach acid?

Answer 22

Competitively and very selectively block the H2 receptors on parietal cells

Inhibits all acid secretion but the highest efficacy is nocturnal

Question 23

What does a bismuth compound do?

Answer 23

• coats and erosions and ulcers
• stimulates prostaglandin production
• stimulates mucous and bicarbonate secretion
• decreases GI secretions to treat diarrhea
• direct antimicrobial effects

Question 24

How does loperamide work to treat diarrhea?

Answer 24

It is an opioid receptor agonist that reduces tone of GI smooth muscle to cause constipation

Limited CNS effects

Question 25

What are the treatment options available for constipation?

Answer 25

• bulk forming laxatives
• lubricant laxatives (glycerin suppositories)
• stool softeners
• osmotic laxatives
• stimulant laxatives

Question 26

What receptors are involved in N/V and how do you treat it?

Answer 26

5-HT3 receptors

NK1 receptors

Anticholinergic/antihistamine

D2 receptor

We need to antagonize these receptors; alternative treatments include cannbinoids, benzodiazapines and phenothiazines

Question 27

What is the difference between transient, short term and chronic/persistent insomnia?

Answer 27

Transient → less than 1 week

Short term → 4 episodes within 12 weeks

Chronic → greater than 3 months

Question 28

Ephedrine has a mechanism of action most similar to which drug?

Answer 28

Amphetamines

think → Ephedrine is a decongestant, decongestants are stimulants, amphetamines are CNS stimulants

Question 29

If rebound congestion occurs, how can it be managed?

Answer 29

Slowly tapering off nasal spray being used and replace with saline spray

Question 30

Decongestants act via _____ to cause _____.

Answer 30

1. Αlpha 1 receptors
2. Vasoconstriction

Question 31

List 3 non-pharmacological interventions you might suggest a patient try before using medications to promote sleep

Answer 31

• limit caffeine
• limit napping during the day
• reduce screen time before bed
• reduce light and noise
• use the bedroom only for sleeping

Question 32

Loperamide is typically dosed at 2mg. Why might an individual take much larger doses?

Answer 32

Loperamide is used to treat diarrhea by reducing the tone of GI smooth muscle and is structurally similar to opioids.

Although it has limited crossing of the blood-brain barrier, someone might take a lot more to get the central opioid effects.

Question 33

Histamine H3 receptors are analogues to which receptors in the adrenergic system?

Answer 33

Αlpha 2 → autoreceptors that regulate the feedback

Question 34

What is the major difference between first and second generation antihistamines?

Answer 34

Ability to cross the blood-brain barrier

Question 35

What is Bismuth used for?

Answer 35

• coat erosions and ulcers
• stimulate prostaglandin production
• stimulate mucous and bicarbonate secretion
• decreases GI secretions to treat diarrhea
• direct antimicrobial effects (against H pylori)

Question 36

What is Clarithromycin?

Answer 36

Antibiotic and can be used in combination with anti-ulcer medications to precent certain types of stomach ulcers

Question 37

What is Cimetide/cimetidine?

Answer 37

Type of antihistamine that blocks the release of stomach acid

Used to treat ulcers of the stomach and intestines and to prevent them from coming back after healing